目的：利用NMR的代谢组学方法比较慢性轻度不可预知应激抑郁模型（CUMS）与慢性束缚应激抑郁模型（CRS），为抗抑郁中药新药的研究提供模型参考。方法：选用SD雄性大鼠制作CUMS模型与CRS模型，以大鼠旷场行为、体重以及糖水偏爱作为常规指标，并采用代谢组学技术对实验21 d大鼠尿液进行NMR数据采集，运用SPSS，MatLab7.5，SIMCA-P软件对数据进行分析。结果：行为学显示，与正常组相比，CUMS组除水平运动外，各种常规指标差异均有统计学意义（P＜0.05），CRS组大鼠水平穿越格数、竖立次数和理毛次数等指标直观上都减少，中央格停留时间延长，粪便粒数增加，但是无统计意义（P＞0.05）；NMR代谢组学分析结果显示，散点图中CUMS组与正常组各样品散点比较集中，CRS组点较分散，介于正常与CUMS组之间。CUMS模型和CRS模型共有的标志物有缬氨酸、亮氨酸、异亮氨酸、甘氨酸、酪氨酸、肌酸，CUMS模型特有标志物为脯氨酸，CRS模型特有标志物为天冬酰胺及精氨酸。结论：行为学及代谢组学均显示CUMS组造模比较成功，CRS组在行为学指标上较差，但运用代谢组学技术显示造模成功，说明代谢组学方法比行为学更灵敏，由于代谢组学技术比常规方法具有灵敏、整体、直观性的优点，因此可用于抑郁模型的筛选。

Objective: To evaluate the chronic unpredictable mild stress (CUMS) model and chronic restraint stress (CRS) model based on metabonomics using NMR. Methods: A total of 18 male Sprague-Dawley (SD) rats were randomly divided into the control group, CUMS group, and CRS group. Taking open-field test, body weight, and sucrose preference test as general indexes during the experimental period, the 21d urine samples were analyzed by NMR. Moreover the data were processed by the SPSS, SIMCA-P, and MATLAB software. Results: The results of behavior changes showed that compared with those of rats in control group, there was significant difference in CUMS group except crossing scores, while those of rats in the CRS group showed a significant difference in dwell time, sucrose preference and consumption. Scores plot of PCA for urine showed that the scatter points of three groups were separated well among groups. Points of CUMS and control group were clustered within groups, while the CRS group scatter points were far away from each other. The shared biomarkers of CUMS model and CRS model have valine, leucine, isoleucine, glycine, tyrosine, creatine, and CUMS model specific biomarker is proline while CRS model specific bioimarkers are aspartic acid and arginine. Conclusion: The behavior changes and metabonomic results show that the CRS model is bad in behavior changes but well in metabonomics, while the CUMS model is successful in each index, which suggests that metabolomics could be more sensitive than behavior test, and has the advantage of sensitive, ensemble, and intuitive, so it can be used for depression model screening.

科技部国际合作项目（2008DFA30430）；国家自然科学基金项目（300772759）；山西省中医药代谢组学国际合作研究联合实验室建设（2008081043）